A trial of combined azacitidine and lenalidomide salvage therapy in patients with acute myeloid leukaemia and myelodysplasia who relapse after allogeneic stem cell transplantation
| ISRCTN | ISRCTN98163167 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN98163167 |
| EudraCT/CTIS number | 2013-002118-11 |
| Secondary identifying numbers | 15789 |
- Submission date
- 25/02/2014
- Registration date
- 25/02/2014
- Last edited
- 09/08/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English Summary
Contact information
Mrs Kathryn Wheeler
Scientific
Scientific
Cancer Research UK Clinical Trials Unit
Institute for Cancer Studies
Edgbaston
Birmingham
B15 2TT
United Kingdom
| Viola@trials.bham.ac.uk |
Study information
| Study design | Non-randomized; Interventional; Design type: Treatment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please contact your consultant for a patient information sheet |
| Scientific title | A phase I trial of combined azacitidine and lenalidomide salvage therapy in patients with acute myeloid leukaemia and myelodysplasia who relapse after allogeneic stem cell transplantation. |
| Study acronym | VIOLA |
| Study hypothesis | Current study hypothesis as of 10/05/2018: Treatment options for patients with acute myeloid leukaemia (AML) or myelodysplasia (MDS) who relapse following an allogeneic stem cell transplant (SCT) are extremely limited and most will die of resistant leukaemia. Two drugs, azacitidine and lenalidomide, have both been shown to have marked clinical activity in patients with AML and MDS who have failed to respond to conventional chemotherapy. Of interest, combined treatment with both azacitidine and lenalidomide appears to increase the response rate in patients with AML and MDS. Importantly, a number of small studies have demonstrated that both azacitidine and lenalidomide when administered alone can also be clinically active in patients who relapse after a stem cell transplant. To date however, combined treatment with azacitidine and lenalidomide has never been examined in this important patient population. In this study, we plan to determine the best tolerated combined dose of azacitidine and lenalidomide in patients who have relapsed after an allogeneic stem cell transplant. The information produced will inform the design of future clinical trials in patients with AML and MDS whose disease has relapsed after an allogeneic transplant. The trial will run in approximately 6 hospitals in the UK. Approximately 27 patients will be recruited to this phase I trial. Previous study hypothesis: Treatment options for patients with acute myeloid leukaemia (AML) who relapse following an allogeneic stem cell transplant (SCT) are extremely limited and most will die of resistant leukaemia. Two drugs, azacitidine and lenalidomide, have both been shown to have marked clinical activity in patients with AML who have failed to respond to conventional chemotherapy. Of interest, combined treatment with both azacitidine and lenalidomide appears to increase the response rate in patients with AML. Importantly, a number of small studies have demonstrated that both azacitidine and lenalidomide when administered alone can also be clinically active in patients who relapse after a stem cell transplant. To date however, combined treatment with azacitidine and lenalidomide has never been examined in this important patient population. In this study, we plan to determine the best tolerated combined dose of azacitidine and lenalidomide in patients who have relapsed after an allogeneic stem cell transplant. The information produced will inform the design of future clinical trials in patients with AML whose disease has relapsed after an allogeneic transplant. The trial will run in approximately 6 hospitals in the UK. Approximately 27 patients will be recruited to this phase 1 trial. More details can be found at: http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=15789 |
| Ethics approval(s) | NRES Committee South Central - Oxford B, 21/01/2014, ref. 13/SC/0581 |
| Condition | Topic: National Cancer Research Network; Subtopic: Haematological Oncology; Disease: Leukaemia (acute myeloid) |
| Intervention | Adverse event discussion, Adverse event discussion 10 minutes. 10 minutes with the doctor (with research nurse if available) within the haematology department; Azacitidine administration, Azacitidine (IMP 1) administration - Azacitidine will be administered by a research nurse/chemotherapy nurse in the haematology department - 20 mins Bone marrow, A trained doctor will perform bone marrow aspirations on the designated haematology ward/day unit/department - 45 mins. Discussion and consent, Initial trial discussion and full written informed consent. 1 hour with the doctor (with research nurse if available) within the haematology department; Discussion of GVHD, Discussion of graft versus host disease symptoms 10 minutes with the doctor (with research nurse if available) within the haematology dept Electrocardiogram (ECG), An ECG will be performed by a research nurse in the haematology/cardiology department - 15 mins Lenalidomide administration, Lenalidomide (IMP 2) administration - Patients will receive oral capsule(s) of lenalidomide. They will take this medication themselves at home at their convenience; Lenalidomide Education, Lenalidomide Education and Guidance Counselling - 15 mins with the doctor (with research nurse if available) within the haematology department; Medical history, Medical history and demographic data discussion. 30 minutes with the doctor (with research nurse if available) within the haematology department; Patient Diary, Completion of patient diary - Patients will be asked to keep a medication diary from day 10-day 42 of each cycle of therapy (to be completed at the patients convenience).; Physical examination, Physical examination and vital signs. A doctor will perform a physical exam and a research nurse will perform and assessment of vital signs in the haematology department - 15 mins; Pregnancy test, Up to 16 pregnancy tests will be required for women of childbearing potential depending on their menstrual pattern. The tests will be performed in the haematology department by a research nurse - 5 mins; Venepuncture, Venepuncture for haematology and biochemistry assessments. Blood samples will be collected either by a research nurse or phlebotomist in the haematology department - 5 minutes.; Venepuncture for research, Venepuncture for research samples - Blood samples for research will be collected by the research - nurse in the haematology department- 5 mins; Follow Up Length: 12 month(s) |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | azactidine, lenalidomide |
| Primary outcome measure | Maximum tolerated dose (MTD); Timepoint(s): Maximum tolerated dose (MTD) of lenalidomide in combination with azacitidine in patients with relaps |
| Secondary outcome measures | 1. Best response rate after combined lenalidomide and azacitidine salvage therapy; Timepoint(s): After combined lenalidomide and azacitidine salvage therapy 2. Overall survival; Timepoint(s): Registration - 1yr post trial treatment 3. Tolerability and safety of lenalidomide in combination with azacitidine; Timepoint(s): Each cycle |
| Overall study start date | 05/02/2014 |
| Overall study end date | 31/12/2018 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 30; UK Sample Size: 30 |
| Total final enrolment | 31 |
| Participant inclusion criteria | Current inclusion criteria as of 10/05/2018: 1. Patients with relapsed AML or MDS following an alemtuzumab- or anti-thymocyte globulin (ATG)-based reduced intensity conditioned allogeneic stem cell transplant using a sibling or unrelated donor 2. Patients able to receive treatment as an outpatient 3. Patients must be willing to comply with the lenalidomide risk management programme 4. Patients must have given written informed consent 5. Patients willing and able to comply with scheduled study visits and laboratory tests Previous inclusion criteria: 1. Patients with relapsed AML following an alemtuzumab or anti-thymocyte globulin (ATG)-based reduced intensity conditioned allogeneic stem cell transplant using a sibling or unrelated donor 2. Patients able to receive treatment as an outpatient 3. Patients must be willing to comply with the lenalidomide risk management programme 4. Patients must have given written informed consent 5. Patients willing and able to comply with scheduled study visits and laboratory tests |
| Participant exclusion criteria | 1. Patients with active acute or chronic extensive graft-versus-host-disease (GvHD), or a history of grade 3 or 4 GvHD 2. Patients with hepatic or renal impairment defined as follows: Total bilirubin ≥ 2.5 x upper limit of normal (ULN)* Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) ≥ 3.0 x ULN Estimated Glomerular Filtration Rate (eGFR) ≤ 40mls/min *Patients with elevated bilirubin due to Gilbert's syndrome are eligible 3. Patients who have received anti-tumour therapies, including prior experimental agents or approved anti-tumour small molecules and biologics, within 28 days before the start of protocol treatment 4. Patients with active symptomatic fungal, bacterial, and/or viral infection 5. Patients with contraindications to receiving azacitidine or lenalidomide 6. Patients with any other condition that in the Investigators opinion would affect the patient's participation in the trial |
| Recruitment start date | 05/02/2014 |
| Recruitment end date | 01/02/2017 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Cancer Research UK Clinical Trials Unit
Birmingham
B15 2TT
United Kingdom
B15 2TT
United Kingdom
Sponsor information
University of Birmingham (UK)
University/education
University/education
Edgbaston
Birmingham
B15 2TT
England
United Kingdom
"ROR" |
https://ror.org/03angcq70 |
|---|
Funders
Funder type
Charity
Leukaemia & Lymphoma Research (UK); Grant Codes: 13019
No information available
Results and Publications
| Intention to publish date | 01/03/2019 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Other |
| Publication and dissemination plan | A publication is in preparation with aims to submit by 01/03/2019. |
| IPD sharing plan | The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Plain English results | No | Yes | |||
| Funder report results | version 1.0a | 31/10/2016 | 09/08/2021 | No | No |
| Results article | 17/01/2019 | 09/08/2021 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No |
Additional files
Editorial Notes
09/08/2021: Publication reference, report and total final enrolment added.
25/03/2020: Cancer Research UK lay results summary link added to Results (plain English).
01/11/2018: The intention to publish date was changed from 31/03/2018 to 01/03/2019.
10/05/2018: The following changes have been made to reflect the inclusion of patients with MDS:
1. The participant inclusion criteria have been changed.
2. The public title has been changed from "A trial of combined azactidine and lenalidomide salvage therapy in patients with acute myeloid leukaemia who relapse after allogeneic stem cell transplantation" to "A trial of combined azacitidine and lenalidomide salvage therapy in patients with acute myeloid leukaemia and myelodysplasia who relapse after allogeneic stem cell transplantation".
3. The scientific title has been changed from "A Phase I trial of combined azactidine and lenalidomide salvage therapy in patients with acute myeloid leukaemia who relapse after allogeneic stem cell transplantation" to "A phase I trial of combined azacitidine and lenalidomide salvage therapy in patients with acute myeloid leukaemia and myelodysplasia who relapse after allogeneic stem cell transplantation".
4. The study hypothesis has been changed.
23/02/2018: The overall trial end date has been updated from 01/02/2017 to 31/12/2018. The publication and dissemination plans have been added and the participant level data sharing statement has been added.
